Abstracts
3427189
(#25) Steady-State Bioequivalence of Novel Once-Daily Lithium Carbonate Extended-Release 900 Milligrams Bi-Layer Matrix Versus Twice-Daily 450 Milligrams: A Randomized Crossover Study in Fed Healthy Adults
Abstract: Purpose: This study evaluated steady-state bioequivalence of a novel once-daily (QD) lithium carbonate extended-release (XR) 900 mg formulation versus a two-times-daily (BID) lithium carbonate extended-release (ER) 450 mg reference product under fed conditions. Safety and tolerability were also assessed.
Methods: This open-label, randomized, two-way crossover bioequivalence study was conducted in healthy adults. Participants received each treatment for 8 consecutive days under fed conditions, with crossover to the alternate treatment. Plasma lithium concentrations from 49 blood samples per subject were quantified using a validated ICP-OES method. Primary pharmacokinetic (PK) parameters included Cmax,ss, AUC0-τ,ss, and Cmin,ss. Bioequivalence was assessed using ln-transformed PK parameters and 90% confidence intervals (CIs) for geometric least squares mean ratios.
Results: Thirty-one participants completed both study periods, with steady state confirmed before Day 8 PK assessments. Mean (±SD) Cmax,ss was 6889.1 ± 1549.0 ng/mL (QD XR) versus 6747.3 ± 1370.7 ng/mL (BID ER). Mean AUC0-τ,ss was 119,593.6 ± 27,858.4 hr*ng/mL (QD XR) versus 122,017.4 ± 25,590.3 (BID ER). Median Tmax,ss was 8.0 h (QD XR) versus 5.0 h (BID ER). Geometric least squares mean ratios were 101.45% (Cmax,ss), 97.30% (AUC0-τ,ss), and 86.84% (Cmin,ss). All 90% CIs for ln-transformed primary PK parameters fell within the 80.0%-125.0% bioequivalence acceptance criteria. Treatments were well tolerated.
Conclusions: The novel QD lithium carbonate XR 900 mg formulation was bioequivalent to FDA-approved BID lithium carbonate ER 450 mg at steady state under fed conditions following 8-day multiple-dose administration, supporting a simplified once-daily dosing regimen with a smoother peak/trough PK profile.
Short Description: This randomized, open-label, two-way crossover study evaluated the steady-state bioequivalence of a novel once-daily lithium carbonate extended-release 900 mg formulation versus a twice-daily 450 mg reference product under fed conditions in healthy adults. Participants received each treatment for 8 days. All primary pharmacokinetic (PK) parameters met bioequivalence acceptance criteria (90% confidence intervals within 80.0%-125.0%), and both treatments were well tolerated. These findings support a simplified once-daily dosing regimen with a smoother peak/trough PK profile.
Name of Sponsoring Organization(s):
Methods: This open-label, randomized, two-way crossover bioequivalence study was conducted in healthy adults. Participants received each treatment for 8 consecutive days under fed conditions, with crossover to the alternate treatment. Plasma lithium concentrations from 49 blood samples per subject were quantified using a validated ICP-OES method. Primary pharmacokinetic (PK) parameters included Cmax,ss, AUC0-τ,ss, and Cmin,ss. Bioequivalence was assessed using ln-transformed PK parameters and 90% confidence intervals (CIs) for geometric least squares mean ratios.
Results: Thirty-one participants completed both study periods, with steady state confirmed before Day 8 PK assessments. Mean (±SD) Cmax,ss was 6889.1 ± 1549.0 ng/mL (QD XR) versus 6747.3 ± 1370.7 ng/mL (BID ER). Mean AUC0-τ,ss was 119,593.6 ± 27,858.4 hr*ng/mL (QD XR) versus 122,017.4 ± 25,590.3 (BID ER). Median Tmax,ss was 8.0 h (QD XR) versus 5.0 h (BID ER). Geometric least squares mean ratios were 101.45% (Cmax,ss), 97.30% (AUC0-τ,ss), and 86.84% (Cmin,ss). All 90% CIs for ln-transformed primary PK parameters fell within the 80.0%-125.0% bioequivalence acceptance criteria. Treatments were well tolerated.
Conclusions: The novel QD lithium carbonate XR 900 mg formulation was bioequivalent to FDA-approved BID lithium carbonate ER 450 mg at steady state under fed conditions following 8-day multiple-dose administration, supporting a simplified once-daily dosing regimen with a smoother peak/trough PK profile.
Short Description: This randomized, open-label, two-way crossover study evaluated the steady-state bioequivalence of a novel once-daily lithium carbonate extended-release 900 mg formulation versus a twice-daily 450 mg reference product under fed conditions in healthy adults. Participants received each treatment for 8 days. All primary pharmacokinetic (PK) parameters met bioequivalence acceptance criteria (90% confidence intervals within 80.0%-125.0%), and both treatments were well tolerated. These findings support a simplified once-daily dosing regimen with a smoother peak/trough PK profile.
Name of Sponsoring Organization(s):
